It’s day one in Prof. Andrew Walsh’s “Contemporary Concepts in Pharmaceutical Validation" class, in the Graduate program in Pharmaceutical Manufacturing and Engineering at Stevens Institute of Technology, and the professor sets the bar high: “You will become the next generation of leaders in the industry,” he pronounces.
Walsh goes on to explain that his course will prepare the students for the most demanding challenges of bringing the drugs of the future to market. Work hard and apply yourself, he tells them, and you’ll walk away ready to transform the way that drugs are made . . . But you just might have to wait a few years to get started.
Walsh’s class is ahead of the curve. It teaches the science- and risk-based principles of Quality by Design, but few of these principles are well entrenched within the industry. Walsh cautions students that they are joining an industry in the midst of change, but resistant to it. “As you know, the world didn't go from flat to round in a day,” he says.
While the industry is begrudgingly warming up to QbD, Walsh says his students are comfortable with it, at least in theory. “Most of my students do not carry any industry baggage with them,” he says. “They understand QbD concepts and accept them. But I warn them that they probably won't see what I teach them in practice for about 5-10 years.”
Students—a mix of graduate pharmacy students, engineers, and others—give the course high marks. They enter the class with what Walsh calls a “recipe level” of understanding as to how drugs are made, and leave with a “high process understanding level.” A main goal of the course is to learn about the sources of variation in a manufacturing process and figure out ways to control them. “They’re getting all the background they will eventually need,” Walsh says, “even though they may be drowning in it now and can’t see that.”
In other words, the course is a bear. For one thing, it’s heavy on statistics. Most of the students have had some statistical work in their undergraduate days—“they certainly know what the mean and standard deviation are,” Walsh says—but that’s about where it ends.
Risk analysis is another tough nut. Students understand risk conceptually, Walsh says, but not quantitatively. Walsh spends several classes discussing the fundamentals of risk management and risk assessment, and then requires FMEA analysis as part of their coursework and final projects. Even though most students are far from mastering QbD, Walsh is helping to construct a template for QbD thinking within students’ minds.
The class project: Launch your own drug. Students are divided into teams of six, and each selects a function: Project Manager, Project Engineer, Process Development Scientist, Lab Supervisor, Validation Engineer, or QA Engineer. Their group project, due at the end of the semester, is to take a solid dosage product from development through process validation to launch, prepare the validation package, incorporating elements of drug product development taught throughout the semester.
“They have production goals and quality requirements,” Walsh says. He has them develop Analytical Methods and conduct Gage R&Rs on them, perform Design of Experiments on pre-blends and on cleaning procedures, FMEA’s on equipment and process, conduct Cleaning and Cleaning Validation (“swabs and all,” Walsh says), and so on.
He also introduces Process Analytical Technologies (PAT) at the drying step: students use thermocouples and a data logger to monitor the internal temperature of the product to determine the drying endpoint.
“They have to develop all their methods, qualify all the equipment and validate the process creating whatever Masterplans, Fishbone diagrams, FMEAs, Protocols, Batch Records, SOPs and Reports are needed and hand in a Validation Package at the end,” he says. Walsh reviews the entire package as part of a Pre-Approval Inspection (PAI).
Walsh also plays the roles of VP of Operations, VP of Quality, Director of Validation etc., and as such will throw students a few real-world challenges. To the QA supervisor, he implores, “Deadlines mean nothing to you. Quality and compliance come first!” To the Project Manager, “Deadlines are critical!” Each Team Member is given goals that are not necessarily aligned with their other Team Members’ goals. Walsh gives the Project Manager a stretch goal that’s nearly impossible to meet. He then sits back and observes. Challenges are thrown in along the way too; this semester included the roll out of an Electronic Document Management System in mid project. Needless to say the project experience is anything but smooth and easy.
Students can get a little testy with one another, Walsh says, but that’s all part of the plan. The last Lecture of the class is devoted to soft skills - Team Dynamics, Emotional Intelligence, Meyers-Briggs, Conflict Modes of Behavior, and the like. Walsh spent many years in the industry himself, working on projects with Johnson & Johnson, Schering-Plough, and Hoffmann-LaRoche, and has learned the value of learning people skills and teamwork.
And at the end of the semester, they eat. The “drugs” that students make are in fact chocolate chip cookies. The process of making chocolate chip cookies is just like making a solid dosage form, Walsh says, without having to purchase any APIs and excipients or disposing of them.
In the future, Walsh would like to have students make rudimentary drug products. He’s been negotiating with manufacturers for hand-me-down equipment. (Any donors out there?) Until then, let them make cookies.
As they walk out the door, do these students really believe they are the leaders of tomorrow, the vanguard of a new era within the pharmaceutical industry? Not exactly, says Walsh. “But what they don’t realize is, someone’s gotta do it.”
Editor’s Note: Stevens is hosting a joint conference with the New Jersey chapter of ISPE at its Hoboken campus on June 17th. There will be vendor displays and presentations from industry and academia on various topics, including QbD and PAT. For more information, contact Prof. Walsh at Andrew.Walsh@stevens.edu.